Seroatlas · Human Serome Atlas

ZIC2

Zinc finger protein ZIC 2

Also known as: HPE5, ZIC2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O95409
Gene
ZIC2
Ensembl
ENSG00000043355
Chromosome
13
Canonical length
532 aa
Protein class
Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors
Subcellular location
Nuclear bodies

OverviewNCBI Gene

This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

532 residues, UniProt reviewed canonical sequence.

>O95409|ZIC2
     1  MLLDAGPQFP AIGVGSFARH HHHSAAAAAA AAAEMQDREL SLAAAQNGFV DSAAAHMGAF
    61  KLNPGAHELS PGQSSAFTSQ GPGAYPGSAA AAAAAAALGP HAAHVGSYSG PPFNSTRDFL
   121  FRSRGFGDSA PGGGQHGLFG PGAGGLHHAH SDAQGHLLFP GLPEQHGPHG SQNVLNGQMR
   181  LGLPGEVFGR SEQYRQVASP RTDPYSAAQL HNQYGPMNMN MGMNMAAAAA HHHHHHHHHP
   241  GAFFRYMRQQ CIKQELICKW IDPEQLSNPK KSCNKTFSTM HELVTHVSVE HVGGPEQSNH
   301  VCFWEECPRE GKPFKAKYKL VNHIRVHTGE KPFPCPFPGC GKVFARSENL KIHKRTHTGE
   361  KPFQCEFEGC DRRFANSSDR KKHMHVHTSD KPYLCKMCDK SYTHPSSLRK HMKVHESSPQ
   421  GSESSPAASS GYESSTPPGL VSPSAEPQSS SNLSPAAAAA AAAAAAAAAA VSAVHRGGGS
   481  GSGGAGGGSG GGSGSGGGGG GAGGGGGGSS GGGSGTAGGH SGLSSNFNEW YV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZIC2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.63
Highest tissue expression
150 nTPM

Expression across tissuesHPA

Tissue

  • cerebellum: 150 nTPM
  • choroid plexus: 19 nTPM
  • cerebral cortex: 9.5 nTPM
  • hippocampal formation: 7.4 nTPM
  • amygdala: 5.7 nTPM
  • spinal cord: 5.4 nTPM

Single-cell type

  • bergmann glia: 83 nCPM
  • brain excitatory neurons: 48 nCPM
  • choroid plexus epithelial cells: 37 nCPM
  • ependymal cells: 29 nCPM
  • astrocytes: 24 nCPM
  • other brain neurons: 11 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • cerebellum: 255 nTPM
  • choroid plexus: 69 nTPM
  • thalamus: 52 nTPM
  • pons: 43 nTPM
  • basal ganglia: 34 nTPM
  • amygdala: 30 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZIC2.

Disease | AllUniProt

Conditions ZIC2 is implicated in, by any mechanism.

Disease | GeneticClinVar

53 pathogenic / likely-pathogenic of 535 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.27
gnomAD pLI
0.97
gnomAD missense Z
3.21
DepMap mean gene effect
-0.02
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ZIC2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ZIC2 as an antibody target. Whether an autoantibody or antibody against ZIC2 could matter depends on whether native ZIC2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZIC2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ZIC2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ZIC2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

© 2026 · Seroatlas, Discover Oregon LLC · Terms of use

Loading the interactive Seroatlas protein explorer...